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Role of programmed necrosis in ARDS and the following remote organ injury

Research Project

Project/Area Number 17K17062
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Emergency medicine
Research InstitutionYokohama City University

Principal Investigator

Tojo Kentaro  横浜市立大学, 医学部, 講師 (80737552)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsARDS / 細胞死 / ネクローシス / アポトーシス / ネクロプトーシス / 臓器障害 / トランスレーショナルリサーチ
Outline of Final Research Achievements

In the present study, we have demonstrated that necrosis rather than apoptosis is a predominant form of alveolar epithelial cell death in LPS-induced experimental ARDS, and that necroptosis, a form of regulated necrosis, is involved in the alveolar epithelial cell death. Moreover, we have shown that mechanical ventilation with high tidal volume augments alveolar epithelial necrosis activating necroptotic pathway. These results suggest that the alveolar epithelial cell necroptosis is a promising therapeutic target for ARDS.

Academic Significance and Societal Importance of the Research Achievements

重症呼吸不全を引き起こし,致死率の高いARDSにおける肺胞上皮細胞傷害のメカニズムとしては主にアポトーシスに主眼をおいた研究が行われてきた.しかしながら本研究の成果により,アポトーシスよりもむしろネクローシスが病態に寄与している可能性が示され,また制御可能なプログラムされたネクロプトーシスが肺胞上皮細胞死を引き起こしていることが示唆された.本研究の成果はネクロプトーシスを含むネクローシスがARDSに対する有望な治療標的であることを示しており,ネクロプトーシスを標的としたARDS治療法開発に向けたさらなる研究を加速させるものである.

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (5 results)

All 2020 2019 2018

All Journal Article (2 results) (of which Peer Reviewed: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Necrosis Rather Than Apoptosis is the Dominant form of Alveolar Epithelial Cell Death in Lipopolysaccharide-Induced Experimental Acute Respiratory Distress Syndrome Model2020

    • Author(s)
      Tamada Nao、Tojo Kentaro、Yazawa Takuya、Goto Takahisa
    • Journal Title

      Shock

      Volume: 54 Issue: 1 Pages: 128-139

    • DOI

      10.1097/shk.0000000000001425

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 肺胞上皮細胞死からみたARDS2020

    • Author(s)
      玉田尚,東條健太郎
    • Journal Title

      臨床麻酔

      Volume: 44 Pages: 535-544

    • Related Report
      2019 Annual Research Report
  • [Presentation] 高容量換気はARDSにおける肺胞上皮細胞ネクローシスを増強する2019

    • Author(s)
      鶴雄斗,玉田尚,東條健太郎,後藤隆久
    • Organizer
      第47回日本集中治療医学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ARDS における肺胞上皮細胞死はアポトーシス or ネクロー シス?:LPS 誘導性 ARDS モデルを用いた検討2018

    • Author(s)
      玉田尚,東條健太郎,後藤隆久
    • Organizer
      第46回日本集中治療医学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Necrosis, rather than apoptosis, is the dominant type of alveolar epithelial cell death in LPS-induced experimental ARDS2018

    • Author(s)
      Nao Tmada, Kentaro Tojo, Takahisa Goto
    • Organizer
      39th International Symposium on Intensive Care and Emergency Medicine
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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